crossing96/oncoscreening huggingface dataset:
Sex Does Not Affect Survival: A Propensity Score-Matched Comparison in a Homogenous Contemporary Radical Cystectomy Cohort.	OBJECTIVES: To determine whether biological sex affects oncological outcome after extended pelvic lymph node dissection, radical cystectomy, and urinary diversion for muscle-invasive bladder cancer, and to identify risk factors impacting outcome. PATIENTS AND METHODS: We performed a single-center, retrospective observational cohort study with prospective data collection with a propensity score matched population. A total of 1165 consecutive patients from 2000 to 2020, (317 women and 848 men) scheduled for open extended pelvic lymph node dissection, radical cystectomy, and urinary diversion for urothelial bladder cancer were included in the final analysis. Overall Survival (OS), Cancer-Specific-Survival (CSS), and Recurrence-Free-survival (RFS) were assessed with multivariable weighted Cox regression analysis as well as with propensity score matched Cox-Regression. RESULTS: No significant difference was found between sexes regarding OS (HR 1.18, [0.93-1.49], P = .16), CSS (HR 0.87, [0.64-1.18], P = .38), or RFS (HR 0.80, [0.59-1.07], P = .13). These results were confirmed after propensity score matching: female sex was not associated with inferior OS (HR 1.20, [0.91-1.60], P = .19), CSS (HR 1.01, [0.75-1.35], P = .97) or RFS (HR 0.98, [0.75-1.27], P = .86). CONCLUSIONS: We did not find a significant difference in cancer-related outcomes or overall survival after extended pelvic lymph node dissection, open radical cystectomy, and urinary diversion for urothelial cancer between males and females even after adjustment with propensity matching score for multiple factors including oncological parameters, smoking status, and renal function.	bladder
Impact of Neoadjuvant Chemotherapy on Pathologic Downstaging in Patients With Variant Histology Undergoing Radical Cystectomy.	INTRODUCTION: Variant histology (VH) bladder cancer is often associated with poor outcomes and the role of neoadjuvant chemotherapy (NAC) remains incompletely defined. Our objective was to determine comparative pathologic downstaging at radical cystectomy (RC) following NAC for patients with and without VH. PATIENTS AND METHODS: Patients who underwent RC at 2 tertiary referral centers (1996-2018) were included. Patients with VH (sarcomatoid, nested, micropapillary, plasmacytoid) were matched 1:2 to patients with pure urothelial carcinoma by age, sex, clinical T (cT)stage, clinical N (cN)stage, cystectomy year and receipt of NAC. The primary outcome was pathologic downstaging (pT-stage < cT-stage). The differential impact of NAC on pathologic downstaging between VH and non-VH was assessed using multivariable logistic regression with interaction analysis. RESULTS: 225 VH and 437 non-VH patients were included. One hundred twenty-eight of six hundred sixty-two (19.3%) patients experienced downstaging, including 54/121 (44.6%) patients who received NAC and 74/542 (13.2%) patients who did not (P < .01). Rates of downstaging after NAC for subgroups were: 45/78 (57.7%) urothelial, 3/8 (37.5%) sarcomatoid, 2/12 (16.7%) nested, 3/14 (21.4%) micropapillary, and 1/8 (12.5%) plasmacytoid. Collectively, 9/42 (21.4%) of VH patients who received NAC were downstaged. On multivariable analyses, NAC was associated with increased likelihood of downstaging in the overall cohort (OR 5.25, 95% CI, 3.29-8.36, P < .0001) and this effect was not modified by VH versus non-VH histology (P = .13 for interaction). VH patients had worse survival outcomes compared to non-VH (P < 0.01 for all). CONCLUSION: When comparing patients with VH to matched pure urothelial carcinoma controls, VH did not have an adverse effect on downstaging following NAC. VH patients should not be excluded from NAC if otherwise eligible.	bladder
ERVK13-1/miR-873-5p/GNMT Axis Promotes Metastatic Potential in Human Bladder Cancer though Sarcosine Production.	N-methyl-glycine (sarcosine) is known to promote metastatic potential in some cancers; however, its effects on bladder cancer are unclear. T24 cells derived from invasive cancer highly expressed GNMT, and S-adenosyl methionine (SAM) treatment increased sarcosine production, promoting proliferation, invasion, anti-apoptotic survival, sphere formation, and drug resistance. In contrast, RT4 cells derived from non-invasive cancers expressed low GNMT, and SAM treatment did not produce sarcosine and did not promote malignant phenotypes. In T24 cells, the expression of miR-873-5p, which suppresses GNMT expression, was suppressed, and the expression of ERVK13-1, which sponges miR-873-5p, was increased. The growth of subcutaneous tumors, lung metastasis, and intratumoral GNMT expression in SAM-treated nude mice was suppressed in T24 cells with ERVK13-1 knockdown but promoted in RT4 cells treated with miR-873-5p inhibitor. An increase in mouse urinary sarcosine levels was observed to correlate with tumor weight. Immunostaining of 86 human bladder cancer cases showed that GNMT expression was higher in cases with muscle invasion and metastasis. Additionally, urinary sarcosine concentrations increased in cases of muscle invasion. Notably, urinary sarcosine concentration may serve as a marker for muscle invasion in bladder cancer; however, further investigation is necessitated.	bladder
Characterization of a miRNA Signature with Enhanced Diagnostic and Prognostic Power for Patients with Bladder Carcinoma.	Bladder carcinoma is globally among the most prevalent cancers and is associated with a high mortality rate at advanced stages. Its detection relies on invasive diagnostic methods that are unpleasant for the patient. Non-invasive molecular biomarkers, such as miRNAs, could serve as alternatives for early detection and prognosis of this malignancy. We designed a computational approach that combines transcriptome profiling, survival analyses, and calculation of diagnostic power in order to isolate miRNA signatures with high diagnostic and prognostic utility. Our analysis of TCGA-BLCA data from 429 patients yielded one miRNA signature, consisting of five upregulated and three downregulated miRNAs with cumulative diagnostic power that outperforms current diagnostic methods. The same miRNAs have a strong prognostic significance since their expression is associated with the overall survival of bladder cancer patients. We evaluated the expression of this signature in 19 solid cancer types, supporting its unique diagnostic utility for bladder carcinoma. We provide computational evidence regarding the functional implications of this miRNA signature in cell cycle regulation, demonstrating its abundance in body fluids, including peripheral blood and urine. Our study characterized a novel miRNA signature with the potential to serve as a non-invasive method for bladder cancer diagnosis and prognosis.	bladder
Metastatic Penile Squamous Cell Carcinoma Responsive to Enfortumab Vedotin.	Penile squamous cell carcinoma is a rare disease with very limited data to guide treatment decisions. In particular, there is minimal evidence for effective therapies in the metastatic setting. Here, we present a case of metastatic penile squamous cell carcinoma with response to the Nectin-4 inhibitor enfortumab-vedotin-ejfv (EV). EV was selected due to the evidence of the high expression of Nectin-4 in squamous cell carcinomas, including penile carcinoma. The patient had both radiographic and symptomatic improvement after two cycles of treatment, despite having been treated with multiple prior lines of traditional chemotherapy. This case provides support for the use of antibody-drug conjugates (ADC), including EV, in this disease with few other options in the advanced setting. Further studies examining Nectin-4 and ADCs in penile squamous cell carcinoma should be completed, as high-quality evidence is needed to guide treatment after initial progression for these patients.	bladder
Pan-cancer analysis of PLAU indicates its potential prognostic value and correlation with neutrophil infiltration in BLCA.	BACKGROUND: PLAU is known as a selected serine protease converting plasminogen to plasmin. The role of PLAU in the development of pan-cancer, especially bladder urothelial carcinoma (BLCA) remains unclear. METHOD: A variety of online tools and cancer databases, including TCGA, GETx, HPA database, GSCALite, UALCAN, ESTIMATE, CIBERSORT, ssGSEA algorithms and SangerBox website, were applied to investigate the associations between PLAU expression and prognosis, genetic alterations, pathway activation, and tumor immunity in pan-cancer. Through cBioPortal and STITCH platforms, the oncogenic role of PLAU and related targeting medicines in BLCA were also explored. We verified the expression of PLAU in pan-cancer cells and its function in bladder cancer cell lines using wet-lab experiments. RESULTS: PLAU expression levels were significantly higher in most cancer tissues. PLAU had a certain accuracy in the diagnosis of various types of cancers (90 % AUC > 0.700). In BLCA, PLAU has abundant methylated sites and showed statistical differences in clinical features. PLAU was involved in tumor immune infiltration, and especially positively correlated with neutrophil infiltration. High-expressed PLAU indicated poorer prognosis in the BLCA patients receiving Atezolizumab. A high mRNA and protein expression levels of PLAU were observed in pan-cancer cell lines, especially BLCA cells. Knockdown of PLAU inhibited the invasive, proliferative, and aggressive phenotypes of bladder cancer cells. Immunohistochemical staining validated PLAU's higher expression in BLCA tissues than in adjacent non-cancerous tissues. And overexpression of PLAU was associated with more advanced TNM stage, and high infiltrating depth. CONCLUSION: Our study revealed that PLAU can serve as a potential therapeutic target and prognostic marker for various malignancies, especially BLCA.	bladder
NECTIN-4 targeted theranostics for urothelial cancer: getting ready for primetime?	Locally advanced and metastatic urothelial carcinoma (UC) presents a bleak prognosis, with limited treatment options. NECTIN-4, an overexpressed protein in UC, has become a target for therapy. Enfortumab vedotin (EV) gained Food and Drug Administration approval for advanced UC treatment, but patient selection based on NECTIN-4 expression remains challenging. In the study under evaluation, Duan et al. introduced a novel PET/CT imaging approach using (68)Ga-N188, a molecular probe, to visualize NECTIN-4 expression in UC. Their study encompassed preclinical evaluations and translational assessments in both healthy individuals and UC patients. Results demonstrated the potential of (68)Ga-N188 in identifying NECTIN-4 expression in UC lesions. Additionally, the study utilized long axial field-of-view (LAFOV) PET/CT, enhancing sensitivity and enabling dynamic studies for improved radiopharmaceutical evaluation. In summary, the study from Duan and colleagues introduces a promising molecular imaging technique that could aid in patient selection for EV therapy and the development of targeted drugs for UC. It also highlights the potential of LAFOV PET/CT in enhancing imaging precision and expanding future therapeutic possibilities for UC.	bladder
Postmarketing Safety of Sacituzumab Govitecan: A Pharmacovigilance Study Based on the FDA Adverse Event Reporting System.	Sacituzumab govitecan is widely used for the treatment of breast cancer and urothelial carcinoma, but available information regarding adverse events (AEs) is limited. We aim to explore the AE induced by sacituzumab govitecan by mining the FDA Adverse Event Reporting System (FAERS) database. The association between sacituzumab govitecan and AEs was evaluated using the information component. A multivariate logistic regression analysis was conducted for all identified signals to explore the risk factors associated with AEs leading to hospitalization. In total, 1,884 reports related to sacituzumab govitecan were retrieved, and 114 AE signals involving 20 systems were identified. The median time for onset of AEs was ~ 6-7 days after initiating treatment with sacituzumab govitecan, with over 80% of AEs occurring within 30 days. Subgroup analysis revealed that 14 signals were reported in men and 110 in women. There were 58 signals reported in patients under 65 following the use of sacituzumab govitecan, 59 signals in patients over 65, and 31 signals were present in both groups. Multivariable analysis showed that being male and the occurrence of colitis, pneumonitis, febrile neutropenia, pyrexia, sepsis, dehydration, and diarrhea were risk factors leading to hospitalization with an area under the curve (AUC) of 0.89. Additionally, sensitivity analysis revealed that this study had good robustness. This is the first retrospective analysis based on FAERS to review the safety of sacituzumab govitecan. The results highlight the need to closely monitor adverse reactions such as neutropenia, diarrhea, colitis, and sepsis when using sacituzumab govitecan.	bladder
Quinolone Prophylaxis in Conjunction with Bacillus Calmette-Guérin Instillations for Bladder Cancer: Time To Reconsider the Evidence and Open the Quinolone Box?	Adjuvant bacillus Calmette-Guérin (BCG) instillations represent a cornerstone in the treatment of non-muscle-invasive bladder cancer. Instillation schedule and dose modifications have been evaluated in efforts to reduce the incidence of adverse events (AEs), but none so far has the same treatment efficacy as the full-dose recommended schedule. It has been shown that prophylactic quinolone use in conjunction with BCG instillations reduces AE incidence and improves timely completion of instillation regimens and patient survival. However, the European Medicines Agency imposed restrictions on the use of quinolones in 2019 because of side effects. Nevertheless, rational use of quinolone prophylaxis could be considered for selected individuals treated with BCG without risk factors for quinolone-associated side effects in conjunction with patient information about side-effect symptoms. PATIENT SUMMARY: Bladder instillations of BCG (bacillus Calmette-Guérin) are used in the treatment of non-muscle-invasive bladder cancer. Antibiotics from the quinolone class can reduce the adverse effects of BCG and help patients in completing the treatment course; however, these antibiotics have their own side effects. Our mini review suggests that the antibiotics could be used in selective cases if patients are given adequate information on these side effects and their symptoms.	bladder
The complementary and alternative roles of elemene injection in cancer: An umbrella review.	BACKGROUND: In the past, many meta-analyses (MAs) suggested that elemene injection (EI) played a complementary and alternative role in cancer treatment. However, some results were contradictory and a lot of evidences weren't classified. Thus, their clinical guidance effect was very limited. METHODS: Two reviewers independently retrieved 8 databases from their origin to May 19, 2023 and appropriate MAs were taken into consideration. A pooled analysis was conducted to merge results extracted from trials of included MAs. The methodological quality of MAs and the evidence certainty of pooled results were assessed. RESULTS: 31 MAs were taken into analysis with poor methodological quality. The main weaknesses were in the areas of heterogeneity analysis, bias risk, and literature selection. According to the present evidence, on the one hand, compared with conventional treatment (CT) alone, EI combined with CT may significantly enhance short-term or long-term efficacy and reduce adverse reactions caused by CT in multiple cancers. On the other hand, using EI alone also can improve ORR in the malignant (pleural) effusion and lessen the recurrence rate in bladder cancer obviously with fewer adverse reactions compared with CT alone. However, this evidence was rated as moderate to very low certainty mainly due to the risk of bias in clinical trials. CONCLUSION: EI may be a viable medication for the treatment of cancer although more convincing trials are still required to demonstrate its alternative and complementary benefits. Besides, it seems to have a broad potential for further development in immunotherapy, drug delivery technique, and predictive factor.	bladder
ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer.	Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair-targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss alters the immune microenvironment and improves anti-PD1 response in preclinical bladder models but is not associated with improved anti-PD1/PD-L1 response in clinical cohorts. Last, we show that ATM expression by immunohistochemistry is strongly correlated with response to chemoradiotherapy. Together, these data define a potential role for ATM as a predictive biomarker in bladder cancer.	bladder
Molecular characterization of plasmacytoid urothelial carcinoma and the impact on treatment implications.	Bladder cancer researchers and clinicians have increasingly viewed tumor biology through the lens of genomic and molecular alterations, drastically improving our knowledge of the underlying disease biology. This understanding has led to significant advances in treatment options that allow implementation of a personalized approach to cancer treatment. Large-scale genomic studies initially focused on the most common forms of bladder cancer. However, as genomic and molecular technologies become more widespread and are applied to less common variant histologies, we are gaining additional insight into the unique molecular and genomic characteristics driving the biology of variant histologies of bladder cancer. In this review, we summarize the current state of knowledge of molecular alterations underlying the distinct tumor biology of plasmacytoid urothelial carcinoma and how these alterations may impact treatment options.	bladder
E-Cigarettes and Associated Health Risks: An Update on Cancer Potential.	The potential cancer risk associated with electronic-cigarette (e-cigarette) use is ongoing and remains a subject of debate. E-Cigarettes work by heating a liquid that usually contains nicotine, flavorings, and other chemicals. When the liquid is heated, users inhale an aerosol into their lungs. While e-cigarettes are generally considered less harmful than traditional tobacco products, they still contain potentially harmful chemicals, which can damage DNA and lead to cancer. Several studies have investigated the potential cancer risk associated with e-cigarette use, while other studies have suggested that e-cigarette aerosol may contain carcinogenic chemicals that could increase the risk of lung and bladder cancer in humans. However, these studies are limited in their scope and do not provide conclusive evidence. Overall, the long-term cancer risk associated with e-cigarette use remains uncertain, more research is needed to fully understand the potential risks and benefits of e-cigarettes. However, this review will allow the investigator to get more recent updates about e-cigarettes.	bladder
Abandoning testing for asymptomatic microscopic haematuria in Sweden - a long-term follow-up.	OBJECTIVES: To test the hypothesis that the Swedish national policy of abandoning testing for asymptomatic microscopic haematuria (AMH) introduced in 1999 did not adversely affect the prognosis of patients with urinary bladder cancer. Specific aims were to investigate possible effects on (1) Diagnostic delay as represented by stage distribution at diagnosis, (2) Survival and mortality trends, also in comparison to other countries and (3) National health care costs. MATERIAL AND METHODS: The design was an observational study using open sources on patients included in the Swedish National Bladder Cancer Registry 1997-2016. Outcome measures were: Changes in initial tumour presentation during 5 years after the change and long-term relative survival and mortality in comparison to the other Nordic countries. Costs related to investigations were estimated based on the national price lists. RESULTS: The proportion of patients diagnosed with muscle-invasive bladder cancer decreased following the policy change. The long-term relative 5-year survival increased during the study period. Mortality has remained constant during the period. In comparison to the other Nordic countries, Sweden remains among those with the best outcome despite a more restrictive approach. Cost savings because of the policy change were estimated to be substantial. CONCLUSIONS: Based on open-source registry data, the new restrictive policy was not found to adversely affect the survival of patients with urinary bladder cancer in Sweden. These observations argue against a major negative impact of abandoning further work-up for patients with AMH and may be of use for other countries when revising guidelines. The reduced number of patients undergoing investigation may allow for increased focus and be a relief both for caregivers and the health budget.	bladder
The mutational pattern of homologous recombination repair genes in urothelial carcinoma and its correlation with immunotherapeutic response.	BACKGROUND: The mutational pattern of homologous recombination repair (HRR)-associated gene alterations in Chinese urothelial carcinoma (UC) necessitates comprehensive sequencing efforts, and the clinical implications of HRR gene mutations in UC remain to be elucidated. MATERIALS AND METHODS: We delineated the mutational landscape of 343 Chinese UC patients from West China Hospital and 822 patients from The Cancer Genome Atlas (TCGA) using next-generation sequencing (NGS). Data from 182 metastatic UC patients from MSK-IMPACT cohort were used to assess the association between HRR mutations and immunotherapy efficacy. Comprehensive transcriptomic analysis was performed to explore the impact of HRR mutations on tumor immune microenvironment. RESULTS: Among Chinese UC patients, 34% harbored HRR gene mutations, with BRCA2, ATM, BRCA1, CDK12, and RAD51C being the most prevalently mutated genes. Mutational signatures contributing to UC differed between patients with and without HRR mutations. Signature 22 for exposure to aristolochic acid was only observed in Chinese UC patients. The presence of HRR mutations was correlated with higher tumor mutational burden, neoantigen burden, and PD-L1 expression. Importantly, patients with HRR mutations exhibited significantly improved prognosis following immunotherapy compared to those without HRR mutations. CONCLUSIONS: Our findings provide valuable insights into the genomic landscape of Chinese UC patients and underscore the molecular rationale for utilizing immunotherapy in UC patients with HRR mutations.	bladder